Verfahren zur Biosynthese von spezifisch isotopenmarkierten Sekundärmetaboliten

摘要

The invention relates to a method for biosynthesis of specific isotope-marked secondary metabolites. The invention addresses the problem of developing a method for specific marking of microbial secondary metabolites having stable or radioactive isotopes, by means of which maximum installation and marking rates can be achieved via strongly reduced use of marked precursors. According to the invention, genes of amino acid biosynthesis in the genome of bacterial or fungal secondary metabolite producers are deactivated by means of genetic engineering methods, the final products (amino acids) of which serve as donors of functional groups of secondary metabolites and are partially or completely integrated in the molecular structure of secondary metabolites. The use of isotope-marked substances occurs substantially more specifically according to the invention than in the currently used method of total marking, which is based on an addition of marked amino acids to a culture medium. The method according to the invention can be used for specific marking of a plurality of natural substances. The particular significance of the method lies in the production of inexpensive, reliable reference substances/standards for modern, highly sensitive analytics methods such as SIDA-MS/MS.